Front Matter

106 Oxytocin, Arginine Vasopressin and Autism Spectrum Disorder

Oxytocin and Developmental Neurological Disorders

Many reviews have exhaustively described the involvement of oxytocin in

learning and memory, and in shaping and regulating the social brain. We

believe one of the best reviews is by Grinevich et al. [10]. The strongest line

of evidence supporting the oxytocin system in social behavior, feeding

behavior, and maternal care has been generated via the study of knockout

mice in which either the oxytocin or the oxytocin receptor genes are inacti-

vated (Table 4.1). Mice constitutively lacking oxytocin (Oxt−/−) are unable

to release milk and have impaired social memory [85]. Mice with constitu-

tive ablation of the oxytocin receptor gene (Oxtr−/−) display a behavior very

similar to that of a mouse where oxytocin producing neurons had been

depleted. These animals display social deficits. In addition, although learn-

ing is normal in mice where the oxytocin receptor gene has been deleted

(Oxtr−/− mice), reversal learning is strongly decreased, indicating impaired

cognitive flexibility suggestive of ASD [86]. Importantly, even a 50% loss of

Table 4.1 Abnormal compartments in ASD that share the loci of oxytocin receptors.

Brain region Autistic abnormalities

Amygdala 13–16% enlargement; functional magnetic resonance imaging study

showed that patients with autism did not activate the amygdala when

making mentalistic inferences from the eyes, whilst people without autism

did show amygdala activity

Olfactory Individuals with ASD exhibited impaired, intact, or increased odor

sensitivity. Abnormal responses to tastes, cold, heat, pain, tickle, and itch

were also observed

Nucleus

accumbens

This is involved in reward anticipation and appears to be defective in ASD

BNST BNST processes information and readiness for response to a threat by

maintaining information from a vast connectivity network. Anatomically,

the BNST is sexually dimorphic; it may explain the gender disparity in the

prevalence and treatment of stress‐related psychiatric diseases and as such

should be investigated as a possible target for treatments. Indeed, drug

targets already involve subpopulations of receptors abundant in the BNST

such as serotonin

Periform

cortex

Cytoarchitecture changes in olfactory cortex may underlie olfactory

differences and sensory deficits seen in autism; increased glial cells

Caudate

nucleus

Increased volume of caudate nucleus (enlargement) in medication naïve

individuals

BNST, bed nucleus of the stria terminalis.

Source: Adapted from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4341354/table/T4/.